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Infections due to non-O1/O139 Vibrio cholerae

J Glenn Morris, Jr, MD, MPHTM
Section Editor
Stephen B Calderwood, MD
Deputy Editor
Allyson Bloom, MD


Vibrio cholerae is a highly diverse species, with a worldwide distribution in estuarine environments. Only a small subset of V. cholerae strains carry the requisite genes to cause the disease cholera. In an effort to identify cholera-causing strains, investigators studying the "cholera bacillus" (V. cholerae) in the early 1900s divided strains into two groups: those that agglutinated with serum from cholera patients (designated as being in O group 1, or V. cholerae O1), and those that did not [1]. This latter strain group (most of which consisted of environmental isolates) has been designated, variously, as "non-cholera Vibrios", "non-agglutinating V. cholerae" (also referred to as "NAGs"), or "non-O1 V. cholerae".

Subsequent serologic studies have resulted in the identification of over 200 different O groups within the species V. cholerae. While it is now recognized that serotype does not correlate directly with the ability to cause the disease cholera, use of these serologic designations continues to be useful with almost all cholera-causing strains falling into O group 1 or the recently recognized O group 139 [2]. However, cholera toxin-producing strains of V. cholerae in other serogroups have also been implicated as the cause of outbreaks of cholera-like illness (O141 and O75 in the United States; O37, O10, O12, O6, and O14 strains from other parts of the world) [3-8]. In phylogenetic studies, all cholera-associated strains tend to cluster closely together, consistent with the concept that there is an "epidemic genotype" that includes multiple genes necessary for epidemic disease [9-11].

In general, strains outside of these serogroups (commonly referred to as "non-O1/non-O139 V. cholerae") are non-pathogenic or asymptomatic colonizers in humans, or cause mild, sporadic illness (such a gastroenteritis, wound or ear infections) in otherwise health hosts. However, in persons who are immunocompromised or who have underlying liver disease, non-O1/non-O139 V. cholerae strains are capable of causing severe wound infections or sepsis, with high associated mortality rates.


Non-O1/non-O139 V. cholerae strains tend to be highly diverse genetically, and there is not a single route by which they cause human disease. Occurrence of illness is dependent on the particular combination of possible virulence genes carried by the infecting strain, combined with the health status of the host.

Gastroenteritis — A small number of non-O1/non-O139 V. cholerae strains carry the genes for and produce cholera toxin (CT), the toxin responsible for the dehydrating diarrhea characteristically seen in epidemic cholera [3,12,13]. These strains have been associated with gastroenteritis (which, at times, may be severe) but do not appear capable of causing epidemic cholera. In phylogenetic studies, they do not cluster with V. cholerae strains responsible for epidemic disease and generally lack multiple genes/gene complexes that have been associated with "typical" cholera.

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Literature review current through: Nov 2017. | This topic last updated: Jun 12, 2017.
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  1. Gardner AD, Venkatraman KV. The Antigens of the Cholera Group of Vibrios. J Hyg (Lond) 1935; 35:262.
  2. Nair GB, Ramamurthy T, Bhattacharya SK, et al. Spread of Vibrio cholerae O139 Bengal in India. J Infect Dis 1994; 169:1029.
  3. Li M, Shimada T, Morris JG Jr, et al. Evidence for the emergence of non-O1 and non-O139 Vibrio cholerae strains with pathogenic potential by exchange of O-antigen biosynthesis regions. Infect Immun 2002; 70:2441.
  4. Dalsgaard A, Serichantalergs O, Forslund A, et al. Clinical and environmental isolates of Vibrio cholerae serogroup O141 carry the CTX phage and the genes encoding the toxin-coregulated pili. J Clin Microbiol 2001; 39:4086.
  5. Tobin-D'Angelo M, Smith AR, Bulens SN, et al. Severe diarrhea caused by cholera toxin-producing vibrio cholerae serogroup O75 infections acquired in the southeastern United States. Clin Infect Dis 2008; 47:1035.
  6. Aydanian A, Tang L, Morris JG, et al. Genetic diversity of O-antigen biosynthesis regions in Vibrio cholerae. Appl Environ Microbiol 2011; 77:2247.
  7. Haley BJ, Choi SY, Grim CJ, et al. Genomic and phenotypic characterization of Vibrio cholerae non-O1 isolates from a US Gulf Coast cholera outbreak. PLoS One 2014; 9:e86264.
  8. Crowe SJ, Newton AE, Gould LH, et al. Vibriosis, not cholera: toxigenic Vibrio cholerae non-O1, non-O139 infections in the United States, 1984-2014. Epidemiol Infect 2016; 144:3335.
  9. Rahman MH, Biswas K, Hossain MA, et al. Distribution of genes for virulence and ecological fitness among diverse Vibrio cholerae population in a cholera endemic area: tracking the evolution of pathogenic strains. DNA Cell Biol 2008; 27:347.
  10. Faruque SM, Chowdhury N, Kamruzzaman M, et al. Genetic diversity and virulence potential of environmental Vibrio cholerae population in a cholera-endemic area. Proc Natl Acad Sci U S A 2004; 101:2123.
  11. Aydanian A, Tang L, Chen Y, et al. Genetic relatedness of selected clinical and environmental non-O1/O139 Vibrio cholerae. Int J Infect Dis 2015; 37:152.
  12. Bi K, Miyoshi SI, Tomochika KI, Shinoda S. Detection of virulence associated genes in clinical strains of vibrio mimicus. Microbiol Immunol 2001; 45:613.
  13. Spira WM, Daniel RR, Ahmed QS, et al. Clinical features and pathogenicity of O group 1 non-agglutinating Vibrio cholerae and other vibrios isolated from cases of diarrhea in Dacca, Bangladesh. In: Symposium on Cholera: Karatsu 1978: Proceedings of the 14th Joint Conference U.S.-Japan Cooperative Medical Science Program Cholera Panel, Takeya J, Zinnaka Y (Eds), Ohta-ku, Tokyo 1978. p.137.
  14. Arita M, Takeda T, Honda T, Miwatani T. Purification and characterization of Vibrio cholerae non-O1 heat-stable enterotoxin. Infect Immun 1986; 52:45.
  15. Morris JG Jr, Takeda T, Tall BD, et al. Experimental non-O group 1 Vibrio cholerae gastroenteritis in humans. J Clin Invest 1990; 85:697.
  16. Bagchi K, Echeverria P, Arthur JD, et al. Epidemic of diarrhea caused by Vibrio cholerae non-O1 that produced heat-stable toxin among Khmers in a camp in Thailand. J Clin Microbiol 1993; 31:1315.
  17. Johnson, JA, Salles, CA, Morris, JG Jr. Correlation of heat-stable enterotoxin and capsule type of non-O1 Vibrio cholerae. 32nd Interscience Conference on Antimicrobial Agents and Chemotherapy, Anaheim, California, 11-14 October, 1992.
  18. Chen Y, Johnson JA, Pusch GD, et al. The genome of non-O1 Vibrio cholerae NRT36S demonstrates the presence of pathogenic mechanisms that are distinct from those of O1 Vibrio cholerae. Infect Immun 2007; 75:2645.
  19. Makino K, Oshima K, Kurokawa K, et al. Genome sequence of Vibrio parahaemolyticus: a pathogenic mechanism distinct from that of V cholerae. Lancet 2003; 361:743.
  20. Park KS, Ono T, Rokuda M, et al. Functional characterization of two type III secretion systems of Vibrio parahaemolyticus. Infect Immun 2004; 72:6659.
  21. Okada N, Iida T, Park KS, et al. Identification and characterization of a novel type III secretion system in trh-positive Vibrio parahaemolyticus strain TH3996 reveal genetic lineage and diversity of pathogenic machinery beyond the species level. Infect Immun 2009; 77:904.
  22. Chatterjee S, Ghosh K, Raychoudhuri A, et al. Incidence, virulence factors, and clonality among clinical strains of non-O1, non-O139 Vibrio cholerae isolates from hospitalized diarrheal patients in Kolkata, India. J Clin Microbiol 2009; 47:1087.
  23. Bag PK, Bhowmik P, Hajra TK, et al. Putative virulence traits and pathogenicity of Vibrio cholerae Non-O1, Non-O139 isolates from surface waters in Kolkata, India. Appl Environ Microbiol 2008; 74:5635.
  24. Miyoshi S, Sasahara K, Akamatsu S, et al. Purification and characterization of a hemolysin produced by Vibrio mimicus. Infect Immun 1997; 65:1830.
  25. Nishibuchi M, Janda JM, Ezaki T. The thermostable direct hemolysin gene (tdh) of Vibrio hollisae is dissimilar in prevalence to and phylogenetically distant from the tdh genes of other vibrios: implications in the horizontal transfer of the tdh gene. Microbiol Immunol 1996; 40:59.
  26. Miyake M, Honda T, Miwatani T. Purification and characterization of Vibrio metschnikovii cytolysin. Infect Immun 1988; 56:954.
  27. Johnson, JA, Joseph, A, Panigrahi, P, Morris, JG Jr. Frequency of encapsulated versus unencapsulated strains of non-O1 Vibrio cholerae isolated from patients with septicemia or diarrhea, or from environmental strains. American Society for Microbiology Annual Meeting, New Orleans, Louisiana, May 26-30, 1992.
  28. Johnson JA, Panigrahi P, Morris JG Jr. Non-O1 Vibrio cholerae NRT36S produces a polysaccharide capsule that determines colony morphology, serum resistance, and virulence in mice. Infect Immun 1992; 60:864.
  29. Halpern M, Broza YB, Mittler S, et al. Chironomid egg masses as a natural reservoir of Vibrio cholerae non-O1 and non-O139 in freshwater habitats. Microb Ecol 2004; 47:341.
  30. Morris JG Jr. Non-O group 1 Vibrio cholerae: a look at the epidemiology of an occasional pathogen. Epidemiol Rev 1990; 12:179.
  31. Baker-Austin C, Trinanes JA, Salmenlinna S, et al. Heat Wave-Associated Vibriosis, Sweden and Finland, 2014. Emerg Infect Dis 2016; 22:1216.
  32. Hlady WG, Klontz KC. The epidemiology of Vibrio infections in Florida, 1981-1993. J Infect Dis 1996; 173:1176.
  33. Morris JG Jr, Black RE. Cholera and other vibrioses in the United States. N Engl J Med 1985; 312:343.
  34. Safrin S, Morris JG Jr, Adams M, et al. Non-O:1 Vibrio cholerae bacteremia: case report and review. Rev Infect Dis 1988; 10:1012.
  35. Ko WC, Chuang YC, Huang GC, Hsu SY. Infections due to non-O1 Vibrio cholerae in southern Taiwan: predominance in cirrhotic patients. Clin Infect Dis 1998; 27:774.
  36. Trubiano JA, Lee JY, Valcanis M, et al. Non-O1, non-O139 Vibrio cholerae bacteraemia in an Australian population. Intern Med J 2014; 44:508.
  37. Finch MJ, Valdespino JL, Wells JG, et al. Non-01 Vibrio cholerae infections in Cancun, Mexico. Am J Trop Med Hyg 1987; 36:393.
  38. Varela G, Olarte J, Perez-Miravete A, Filloy L. Failure to find cholera and noncholera vibrios in diarrheal disease in Mexico City, 1966-67. Am J Trop Med Hyg 1971; 20:925.
  39. CDC. National Enteric Disease Surveillance: COVIS Annual Summary, 2014. https://www.cdc.gov/nationalsurveillance/pdfs/covis-annual-summary-2014-508c.pdf (Accessed on May 31, 2017).
  40. Morris JG Jr, Wilson R, Davis BR, et al. Non-O group 1 Vibrio cholerae gastroenteritis in the United States: clinical, epidemiologic, and laboratory characteristics of sporadic cases. Ann Intern Med 1981; 94:656.
  41. Hirk S, Huhulescu S, Allerberger F, et al. Necrotizing fasciitis due to Vibrio cholerae non-O1/non-O139 after exposure to Austrian bathing sites. Wien Klin Wochenschr 2016; 128:141.
  42. Dechet AM, Yu PA, Koram N, Painter J. Nonfoodborne Vibrio infections: an important cause of morbidity and mortality in the United States, 1997-2006. Clin Infect Dis 2008; 46:970.
  43. Chen YT, Tang HJ, Chao CM, Lai CC. Clinical manifestations of non-O1 Vibrio cholerae infections. PLoS One 2015; 10:e0116904.